Global Antigenic Landscape and Vaccine Recommendation Strategy for Low Pathogenic Avian Influenza A(H9N2) Viruses

The sustained circulating of H9N2 avian influenza viruses (AIVs) poses a significant threat for contributing to a new pandemic. Given the temporal and spatial uncertainty in antigenicity of H9N2 AIVs, the immune protection efficiency of vaccines remains challenging. By developing an antigenicity prediction method for H9N2 AIVs, named PREDAC-H9, the global antigenic landscape of H9N2 AIVs was mapped. PREDAC-H9 utilizes the XGBoost model with 14 well-designed features. The XGBoost model was built and evaluated to predict the antigenic relationship between any two viruses with high values of 81.1%, 81.4%, 81.3%, 81.1%, and 89.4% in accuracy, precision, recall, F1 value, and area under curve (AUC), respectively. Then the antigenic correlation network (ACnet) was constructed based on the predicted antigenic relationship for H9N2 AIVs from 1966 to 2022, and ten major antigenic clusters were identified. Of these, four novel clusters were generated in China in the past decade, demonstrating the unique complex situation there. To help tackle this situation, we applied PREDAC-H9 to calculate the cluster-transition determining sites and screen out virus strains with high cross-protective spectrum, thus providing in-silico reference for vaccine recommendation. The proposed model will reduce the clinical monitoring workload and provide useful tool for surveillance and control of H9N2 AIVs.Availability of data and materialsThe data that support the findings of this study are available in the Supplementary Data.